A Single-ascending Dose (Part A) and Repeat-dose (Part B) Study to Investigate the Safety, Pharmacokinetics and Efficacy (Part B Only) of UCB1381 in Healthy Study Participants (Part A) and in Study Participants With Moderate to Severe Atopic Dermatitis (Part B)

UCB

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Atopic Dermatitis

Treatments: Drug: Placebo; Biological: UCB1381

Study type: Interventional

Funder types: Industry

Identifiers

NCT05277571

UP0110

Details and patient eligibility

About

The purpose of the study is to investigate the safety and tolerability of single-ascending doses of UCB1381 (intravenous and subcutaneous) in healthy study participants and after repeat intravenous dosing in study participants with atopic dermatitis. Efficacy will be assessed following repeat intravenous dosing versus placebo in study participants with atopic dermatitis.

Enrollment: 152 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

Part A Healthy study participants

• Participant must be 18 to 55 years of age inclusive at the time of signing the informed consent form (ICF)
• Participant must be overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring
• Participant has a body mass index (BMI) within the range 18 to 30 kg/m2 (inclusive)
• Participant can be male or female and must agree to use contraception

Part B Participants with moderate to severe Atopic dermatitis (AtD)

• Participant must be 18 to 65 years of age inclusive at the time of signing the ICF

• Participant has moderate or severe AtD that has been present for at least 12 months prior to initiating the study (signing of the ICF) and with:

• A validated Investigator Global Assessment (vIGA) score ≥3 at Screening and Baseline

• An Eczema Area and Severity Index (EASI) score of ≥14 at Screening and ≥16 at Baseline

• Pruritis Numerical Rating Scale (NRS) ≥3 at Screening and Baseline

  -≥10 % body surface area (BSA) of AtD involvement at Screening and Baseline

• Either documented recent history (within 6 months before the Screening Visit) of inadequate response to treatment with topical medications (regular use of topical corticosteroids [TCS] or topical calcineurin inhibitors [TCIs]) or when topical treatments are confirmed to be otherwise medically inadvisable (eg, because of important side effects or safety risks)

• Participant has a BMI within the range 18 to 35 kg/m2 (inclusive)

Exclusion criteria

Part A Healthy study participants

• Participant has a history or presence of any medical or psychiatric condition, physical examination finding, laboratory test result, electrocardiogram (ECG), or vital sign that, in the opinion of the investigator, could significantly alter the absorption, metabolism, or elimination of drugs; constitute a risk when taking the study intervention; or interfere with the interpretation of data
• Participant has a known hypersensitivity to any components of the investigational medicinal product (IMP) or other biologic drugs (including humanized monoclonal antibodies (mAbs)), clinically significant drug allergies, or history of severe adverse reactions after drug administration
• Participant has a past history of inflammatory bowel disease (includes Crohn's disease and ulcerative colitis)
• Participant has previously been randomized in this study
• Participant has participated in another study of an IMP or has received any biologic agent (such as mAbs, including marketed drugs and including biologic agents that target interleukin (IL)-13 or IL-22) within the 30 days prior to Screening or 5 half-lives (whichever is longer), if this information can be validated by the investigator

Part B Participants with moderate to severe AtD

• Participant has a history or presence of any medical or psychiatric condition, physical examination finding, laboratory test result, electrocardiogram (ECG), or vital sign that, in the opinion of the investigator, could significantly alter the absorption, metabolism, or elimination of drugs; constitute a risk when taking the study intervention; or interfere with the interpretation of data
• Participant has a known hypersensitivity to any components of the IMP or other biologic drugs (including humanized mAbs), clinically significant drug allergies, or history of severe adverse reactions after drug administration
• Participant has a past history of inflammatory bowel disease (includes Crohn's disease and ulcerative colitis)
• Participant has had pharmaceutically active topical therapies for AtD (including mild topical corticosteroids (TCS)) within 2 weeks of the Baseline Visit (corticosteroids, cyclosporin or other calcineurin inhibitors [eg, tacrolimus, pimecrolimus])
• Participant has received phototherapy or systemic non-biologic therapies for AtD within 4 weeks of the Baseline Visit (including moderate/strong corticosteroids, cyclosporine A or other calcineurin inhibitors, mycophenolate mofetil, azathioprine, methotrexate, or any alternative medicine for AtD, eg, traditional Chinese medicine)
• Participant has previously used a biologic that affects IL-13 or IL-22 pathways, or any JAK inhibitor (including marketed and/or experimental treatments), within 30 days or 5 half-lives (whichever is longer) of the Baseline Visit. Previous use of biologics affecting IL-13 or IL-22 pathways is only accepted if treatment was stopped due to reasons other than inadequate efficacy and safety (eg, administrative reasons, poor convenience, poor access to drug)
• Participant has received any prescription or nonprescription medicines, including over the counter remedies and herbal and dietary supplements (other than vitamins within recommended daily dose limits) within 14 days (or 5 half-lives of the respective drug, whichever is longer) prior to the Baseline Visit, other than contraceptives (oral, implant, or intrauterine devices) or occasional use of analgesics such as paracetamol (acetaminophen, with or without caffeine, with a maximal dose of 4g/day and 10g/14 days) or intranasal corticosteroids for seasonal rhinitis or inhaled bronchodilators and low dose inhaled corticosteroids for mild asthma. In case of uncertainty, the UCB Development Physician should be consulted
• Participant has previously been randomized in this study
• Participant has participated in previous studies with a biologic that affects IL-13 or IL-22 pathways, or any JAK inhibitor (including marketed and/or experimental treatments), within 30 days or 5 half-lives (whichever is longer) of the Baseline Visit. Previous use of biologics affecting IL-13 or IL-22 pathways is only accepted if treatment was stopped due to reasons other than inadequate efficacy and safety (eg, administrative reasons, poor convenience, poor access to drug)
• Participant has participated in another study of an IMP within 30 days or 5 half-lives (whichever is longer) of the Baseline Visit or is currently participating in another study of an IMP

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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152 participants in 12 patient groups, including a placebo group

UCB1381 dosing regime 1 in Part A

Experimental group

Description:

Participants will be randomized to receive a single dose UCB1381 intravenously (iv).

Treatment:

Biological: UCB1381

UCB1381 dosing regime 2 in Part A

Experimental group

Description:

Participants will be randomized to receive a single dose UCB1381 intravenously (iv).

Treatment:

Biological: UCB1381

UCB1381 dosing regime 3 in Part A

Experimental group

Description:

Participants will be randomized to receive a single dose UCB1381 intravenously (iv).

Treatment:

Biological: UCB1381

UCB1381 dosing regime 4 in Part A

Experimental group

Description:

Participants will be randomized to receive a single dose UCB1381 intravenously (iv).

Treatment:

Biological: UCB1381

UCB1381 dosing regime 5 in Part A

Experimental group

Description:

Participants will be randomized to receive a single dose UCB1381 subcutaneously (sc).

Treatment:

Biological: UCB1381

UCB1381 dosing regime 6 in Part A

Experimental group

Description:

Participants will be randomized to receive a single dose UCB1381 subcutaneously (sc).

Treatment:

Biological: UCB1381

UCB1381 dosing regime 7 in Part A

Experimental group

Description:

Participants will be randomized to receive a single dose UCB1381 intravenously (iv).

Treatment:

Biological: UCB1381

UCB1381 dosing regime 8 in Part A

Experimental group

Description:

Participants will be randomized to receive a single dose UCB1381 intravenously (iv).

Treatment:

Biological: UCB1381

UCB1381 dosing regime 9 in Part B

Experimental group

Description:

Participants will be randomized to receive repeated doses UCB1381 intravenously (iv).

Treatment:

Biological: UCB1381

Placebo iv Arm Part A

Placebo Comparator group

Description:

Participants will be randomized to receive a single dose of placebo iv to maintain the blinding.

Treatment:

Drug: Placebo

Placebo sc Arm Part A

Placebo Comparator group

Description:

Participants will be randomized to receive a single dose of placebo sc to maintain the blinding.

Treatment:

Drug: Placebo

Placebo iv Arm Part B

Placebo Comparator group

Description:

Participants will be randomized to receive repeated doses of placebo iv to maintain the blinding.

Treatment:

Drug: Placebo